Carbamazepine-induced severe cutaneous adverse reactions and HLA genotypes in Koreans.

Abstract

BACKGROUND:

Although the US FDA recommends screening for HLA-B*1502 allele in most of Asian ancestry before initiating carbamazepine therapy, the HLA associations with carbamazepine hypersensitivity in non-Chinese Asian populations remain unclear. This study investigated the association between the HLA class I genotype and carbamazepine-induced severe cutaneous adverse reaction (SCAR) in Koreans.

METHODS:

Twenty-four patients who had developed carbamazepine-induced SCAR (7 Stevens-Johnson syndrome (SJS), 17 drug hypersensitivity syndrome (HSS)), 50 carbamazepine-tolerant controls from the Korean Pharmacogenetic Adverse Drug Reaction Research Network and data of 485 Korean general population from a previously published study were recruited. HLA-A, -B, and -C genotyping was performed by direct DNA sequence analysis.

RESULTS:

Only one of the seven SJS patients was positive for the B*1502 allele, but the frequency of B*1511 was much higher in the patients with CBZ-SJS than in the CBZ-tolerant control patients (P=0.011, P(c)=not significant; OR=18.0(2.3-141.2)). The frequencies of A*3101 in carbamazepine-induced HSS and SCAR were significantly higher than those in carbamazepine-tolerant controls (P(c)=0.011, OR=8.8(2.5-30.7) and P(c)=0.013, OR=7.3(2.3-22.5), respectively). The frequencies of B*1511 in carbamazepine-SJS and A*3101 in carbamazepine-HSS/SCAR were significantly higher than those in the general population.

CONCLUSIONS:

HLA-B*1502 does not seem to be an effective predictive marker for carbamazepine-induced SCAR, while HLA-B*1511 and A*3101 was associated with carbamazepine-induced SJS and HSS/SCAR respectively in the Korean population.

• Authors: Sae-Hoon Kim, Kyung Wha Lee, Woo-Jung Song, Sang-Heon Kim, Young-Koo Jee, Sang-Min Lee, Hye-Ryun Kang, Heung-Woo Park, Sang-Heon Cho, Seong-Ho Park, Kyung-Up Min, Yoon-Seok Chang, Adverse Drug Reaction Research Group in Korea
• Journal: Epilepsy research (Epilepsy Res) Vol. 97 Issue 1-2 Pg. 190-7 (Nov 2011) ISSN: 1872-6844 [Electronic] Netherlands
• PMID: 21917426 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2011 Elsevier B.V. All rights reserved.

Chemical References

• Anticonvulsants
• Histocompatibility Antigens Class I
• Carbamazepine

Topics

• Adult
• Aged
• Anticonvulsants (adverse effects)
• Asian People (genetics, statistics & numerical data)
• Carbamazepine (adverse effects)
• Drug Eruptions (ethnology, genetics)
• Epilepsy (drug therapy, ethnology, genetics)
• Female
• Gene Frequency
• Genetic Predisposition to Disease (ethnology, genetics)
• Genotype
• Histocompatibility Antigens Class I (genetics)
• Histocompatibility Testing
• Humans
• Male
• Middle Aged
• Pharmacogenetics (statistics & numerical data)
• Predictive Value of Tests
• Republic of Korea
• Stevens-Johnson Syndrome (chemically induced, ethnology, genetics)
• Young Adult